Pharmacokinetics and Anti-Inflammatory Effects of Intramuscular Betamethasone in Exercised Thoroughbred Horses.

The pharmacokinetics and pharmacodynamics of betamethasone following intra-articular administration to horses have been described; however, studies characterizing intramuscular administration are lacking. Twenty-four horses received an intramuscular dose of 12 mg betamethasone sodium phosphate/betamethasone acetate. Blood and urine were collected at post administration for up to 408 h. Concentrations of betamethasone were determined using LC-MS/MS and pharmacokinetic parameters determined using a Population PK three-compartment model. The duration of pharmacodynamic effects was assessed by measuring changes in cortisol and inflammatory biomarkers utilizing an ex vivo model. The Cmax, Tmax, and terminal half-life of betamethasone were 6.43 ± 1.70 ng/mL, 0.75 (0.5-2.0 h; median and range), and 30.5 ± 20.4 h, respectively. Covariates were not found to have significant effects on the variability of pharmacokinetic parameters. Based on Monte Carlo simulations, for 1000 horses, a detection time of 23 days is recommended for concentrations to fall below the screening limit of 10 pg/mL in 99% of the population. Urine concentrations were above the limit of quantitation in 2/24 horses at 408 h. Suppression of cortisol lasted for 360 h. Effects on inflammatory biomarker production lasted for a prolonged period. An extended withdrawal time for intramuscular administration prior to competition is warranted.